Special Biology Seminar“Prion-Like Propagation of Protein Assemblies in Neurodegenerative Diseases” Ronald Melki Laboratoire d’Enzymologie et Biochimie Structurales, CNRS, Gif-sur-Yvette
Abstract: Misfolded protein aggregates are the hallmark of several neurodegenerative diseases in men. The main protein constituent of these aggregates and the regions within the brain that are affected differ from one neurodegenerative disorder to another. Until recently, the vicious circle consisting of template- driven misfolding of similar proteins over time, spread from one neuron to another and accumulation within the central nervous system of misfolded proteins aggregates that are associated to disease was thought to be restricted to the prion protein PrP. A wide range of recent experimental evidences suggest that other protein aggregates that are the hallmarks of major neurodegenerative diseases spread in a prion-like manner. I will show examples of such behavior. I will discuss the nature of protein assemblies that are infectious and the reasons they are toxic to cells. I will show how one protein, alpha-synuclein, takes advantage of its chameleon properties to assemble into structurally and functionally distinct assemblies, we believe associated to distinct diseases (synucleinopathies). Finally, strategies targeting the propagation of protein assemblies involved in age-related dementias will be presented and the open questions we are facing will be discussed.
Hosts: Prof. Ron Kopito & Prof. Aaron Gitler